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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19477990 A Classifier-based approach to identify genetic similarities between diseases. 2009 Jun 15 MOTIVATION: Genome-wide association studies are commonly used to identify possible associations between genetic variations and diseases. These studies mainly focus on identifying individual single nucleotide polymorphisms (SNPs) potentially linked with one disease of interest. In this work, we introduce a novel methodology that identifies similarities between diseases using information from a large number of SNPs. We separate the diseases for which we have individual genotype data into one reference disease and several query diseases. We train a classifier that distinguishes between individuals that have the reference disease and a set of control individuals. This classifier is then used to classify the individuals that have the query diseases. We can then rank query diseases according to the average classification of the individuals in each disease set, and identify which of the query diseases are more similar to the reference disease. We repeat these classification and comparison steps so that each disease is used once as reference disease. RESULTS: We apply this approach using a decision tree classifier to the genotype data of seven common diseases and two shared control sets provided by the Wellcome Trust Case Control Consortium. We show that this approach identifies the known genetic similarity between type 1 diabetes and rheumatoid arthritis, and identifies a new putative similarity between bipolar disease and hypertension.
20595282 A modified rheumatoid arthritis disease activity score without acute-phase reactants (mDAS 2010 Aug 1 OBJECTIVE: To develop and validate a modified version of the Disease Activity Score with 28 joint count (mDAS28), for use in epidemiological research, when acute-phase reactant values are unavailable. METHODS: In a cross-sectional development cohort (5729 patients), statistically significant predictors of the logarithm of erythrocyte sedimentation rate (lnESR) were identified. After computation of the mDAS28, a cross-sectional validation cohort (5578 patients) was used to evaluate internal, criterion, and construct validities. The ability of the mDAS28 to discriminate between disease states was also assessed. A second validation cohort (longitudinal, 336 pairs of patient visits) was used to assess sensitivity to change. RESULTS: Significant predictors of lnESR included tender and swollen joints with 28 counts, patient's and physician's assessments of global health, and patient's assessment of pain (visual analog scale 0-100 mm) and a physical function (modified Health Assessment Questionnaire 0-3; mHAQ). Satisfactory internal validity (alpha = 0.72) and strong criterion validity compared to the DAS28, the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) (r = 0.87-0.96) were found. Predictive validity was demonstrated by good correlation with the mHAQ (r = 0.58). The mDAS28 showed substantial agreement with the DAS28, SDAI, and CDAI in discriminating between disease states (kappa = 0.70-0.77) and moderate to substantial agreement between response levels (kappa = 0.52-0.73). Both mDAS28 and DAS28 measures classified patients similarly in remission compared to the SDAI and CDAI. The mDAS28 was superior in detecting change (standardized response mean = 0.58) followed by the DAS28, CDAI, and SDAI. CONCLUSION: The mDAS28 is a valid and sensitive tool to assess disease activity in epidemiological research, as an alternative to the DAS28, when acute-phase reactant values are unavailable.
19248128 Rheumatoid arthritis, its treatments, and the risk of tuberculosis in Quebec, Canada. 2009 Mar 15 OBJECTIVE: To determine the risk of tuberculosis (TB) among a cohort of patients with rheumatoid arthritis (RA) in Quebec and assess whether this risk is associated with exposure to nonbiologic disease-modifying antirheumatic drugs (DMARDs). METHODS: We studied a cohort of patients with RA identified from the Quebec provincial physician billing and hospitalization databases for 1980-2003. TB incidence rates were determined for the period 1992-2003 and compared with the general population, standardized for age and sex using the standardized incidence ratio (SIR). Conditional logistic regression was used in a nested case-control analysis to estimate the rate ratio (RR) of TB related to nonbiologic DMARD exposure during the year before the index date. RESULTS: Of the 24,282 patients with RA in the cohort, 50 cases of TB were identified. The standardized incidence rate was 45.8 cases per 100,000 person-years compared with 4.2 cases per 100,000 person-years in the general population of Quebec (SIR 10.9, 95% confidence interval [95% CI] 7.9-15.0). The adjusted RR of TB was 2.4 (95% CI 1.1-5.4) with corticosteroid use and 3.0 (95% CI 1.6-5.8) with nonbiologic DMARD use. CONCLUSION: The age- and sex-standardized incidence rate of TB in RA patients is 10 times that of the general population. At least some of this risk may be related to nonbiologic DMARD and corticosteroid therapies. Our data support the role of TB screening before initiation of any immunosuppressive therapy.
20863813 MDM4 overexpression contributes to synoviocyte proliferation in patients with rheumatoid a 2010 Oct 22 Rheumatoid arthritis (RA) is a chronic autoimmune disease with features of inflammatory cell infiltration, synovial cell invasive proliferation, and ultimately, irreversible joint destruction. It has been reported that the p53 pathway is involved in RA pathogenesis. MDM4/MDMX is a major negative regulator of p53. To determine whether MDM4 contributes to RA pathogenesis, MDM4 mRNA and protein expression were assessed in fibroblast-like synoviocytes (FLS) by real-time PCR, western blotting, and in synovial tissues by immunohistochemistry. Furthermore, MDM4 was knocked down and overexpressed by lentivirus-mediated expression, and the proliferative capacity of FLS was determined by MTS assay. We found that cultured FLS from RA and osteoarthritis (OA) patients exhibited higher levels of MDM4 mRNA and protein expression than those from trauma controls. MDM4 protein was highly expressed in the synovial lining and sublining cells from both types of arthritis. Finally, MDM4 knockdown inhibited the proliferation of RA FLS by enhancing functional p53 levels while MDM4 overexpression promoted the growth of RA FLS by inhibiting p53 effects. Taken together, our results suggest that the abundant expression of MDM4 in FLS may contribute to the hyperplasia phenotype of RA synovial tissues.
19602478 Early rheumatoid arthritis and body composition. 2009 Sep OBJECTIVES: RA is associated with joint destruction and cardiovascular diseases (CVDs). Possible predictors for CVD are early changes in body composition. We therefore evaluated whether lean mass of arms and legs (LMAL), total body fat mass (BFM) or truncal fat distribution (TFD) are altered early in RA, and if so, which factors are associated. METHODS: We included 132 RA patients (95 women) with disease duration of < or =12 months. Disease activity score (DAS28), HAQ, BMI, comorbidity, smoking and medications were recorded. Total and regional lean mass and fat mass were measured with DXA. Data were compared with 132 age- and gender-matched controls, and possibly associated factors were analysed in linear regression models. RESULTS: LMAL was low in patients for both women and men (P = 0.007 and <0.001, respectively). BMI (P = 0.012), BFM (P = 0.014) and TFD (P < 0.001) were higher than expected in RA women. In bivariate analyses, all adjusted for age and current smoking, disease duration was independently associated with low LMAL in women (P = 0.021). High BFM was associated with HAQ x disease duration in men (P = 0.033) and DAS28 in women (P = 0.011). High TFD was associated with a history of diabetes or CVD in men with RA (P = 0.005). CONCLUSIONS: Low LMAL, high BFM and high TFD are present in early RA patients. The long-term significant consequences of these abnormalities need to be determined.
19169621 Increased frequencies of hysterectomy and early menopause in fibromyalgia patients: a comp 2009 May The objective was to determine the relationship between symptoms of fibromyalgia (FM) and early menopause and hysterectomy. We included 115 postmenopausal patients with FM (mean age 54.6 +/- 7.6) and 67 rheumatoid arthritis (RA) patients (mean age 55.5 +/- 9) into our study. All patients were questioned about the severity of their symptoms of FM, anxiety, and depression by using a visual analog scale and FM impact questionnaire. Patients' history of menopause and hysterectomy were recorded. Menopause ( 0.05). FM-related symptoms started in 30 patients (26.1%) with FM with menopause or within the first postmenopausal year. When the clinical features of FM patients whose symptoms started within the first menopausal year were compared to other FM patients; it was observed that the frequency of early menopause was higher in the former group (p = 0.048). Duke anxiety and depression score was higher in patients with hysterectomy whose FM symptoms started within the first year of post-hysterectomy than other FM patients (9.1 +/- 2.7 vs. 6.7 +/- 2.7, p = 0.022). Early menopause and hysterectomy may be one of the factors contributing to the development of FM.
18633128 Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is reversibly 2009 Jun OBJECTIVE: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with similar regulation to collagen type II. As MIA is a small secreted protein, its value as cartilage biomarker in human inflammatory arthritis was assessed. METHODS: MIA tissue distribution was studied by quantitative PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during tumour necrosis factor (TNF)alpha and interleukin (IL)1 blockade in RA. RESULTS: MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA, but not in SpA, and that the levels of TNFalpha and IL1beta were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF blockade or IL1 blockade induced an increase of serum MIA levels. CONCLUSION: The decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA not only drives accelerated cartilage degradation but also suppresses cartilage anabolism. This inflammation-driven suppression is reversible in vivo.
19337708 [Whole-body cryotherapy in patients with inflammatory rheumatic disease. A prospective stu 2009 Mar 15 BACKGROUND: As yet, whole-body cryotherapy is especially used for the therapy of chronic inflammatory arthritis. An analgetic effect has been described in several studies. However, only few data exist concerning the long-term effects of this therapy. PATIENTS AND METHODS: A total of 60 patients with rheumatoid arthritis (n = 48), and ankylosing spondylitis (n = 12) was analyzed. Patients underwent treatment with whole-body cryotherapy twice a day. The average age was 55.7 +/- 10.33. The study group consisted of 48 female and twelve male patients. The average number of therapeutic treatments with cryotherapy was 15.8 +/- 8.37, the average follow-up 63.4 +/- 63.48 days. RESULTS: 13 patients (21.7%) discontinued treatment because of adverse effects. For patients with rheumatoid arthritis, DAS28 (Disease Activity Score) and VAS (visual analog scale) were determined. A significant reduction of both parameters was found (DAS 3.9 +/- 1.22 vs. 3.4 +/- 1.08; p < 0.01; VAS 51.4 +/- 16.62 vs. 37.9 +/- 19.13; p < 0.01). BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) was analyzed for patients with ankylosing spondylitis, and also showed a significant reduction (4.4 +/- 1.91 vs. 3.1 +/- 1.34; p = 0.01). CONCLUSION: Thus, whole-body cryotherapy is an effective option in the concept of treatment of inflammatory rheumatic diseases. The relief of pain allows an intensification of physiotherapy. A significant reduction of pain over a period of 2 months could be shown.
19723321 Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mi 2009 INTRODUCTION: Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The pro-apoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. METHODS: In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. RESULTS: Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P < 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell- or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). CONCLUSION: Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
19664170 More about masitinib. 2009 A dose-escalating phase II trial studied masitinib, an oral tyrosine kinase inhibitor, in 43 patients with rheumatoid arthritis. Masitinib induced American College of Rheumatology (ACR)20, ACR50 and ACR70 responses in 54%, 26% and 8% of patients, respectively. A placebo group was not included. Thirty-seven per cent of the patients withdrew before the 12-week end-point was reached, primarily because of adverse events. These findings are the first on the efficacy of tyrosine kinase inhibition in a sizeable population. Future work should focus on delineating the tyrosine kinase that is most important in maintaining rheumatoid activity and address potential long-term toxicities such as gonadal insufficiency, teratogenicity and cardiotoxicity.
18593757 Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort stud 2009 Apr OBJECTIVES: The "fetal origins of adult disease" hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual's future risk of rheumatoid arthritis (RA). METHODS: The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses' Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18. RESULTS: In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2-3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6). CONCLUSIONS: In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.
20301227 A literature review regarding the management of varicella-zoster virus. 2010 Jun Chickenpox and shingles (varicella-zoster virus [VZV]) pose a threat to individuals who are immunosuppressed and/or have rheumatoid arthritis or another inflammatory musculoskeletal condition. In this paper we present a literature review of the condition, management and prevention.
20934100 Complications of digital and lesser metatarsal surgery. 2010 Oct Complications associated with digital and lesser metatarsal surgical procedures have been well documented in the literature. These complications may stem from systemic medical, structural, biologic, biomechanical, or iatrogenic causes. The surgeon must be cognizant of all potential complications, including ways to prevent them from occurring and how to manage them when they do occur. This article discusses preventative measures through the preoperative evaluation of the patient, and examines the subsets of complications that may occur after lesser ray surgery that pose a particular management challenge, as well as special complications specific to particular operative techniques.
21091389 Lumbar radiculopathy caused by foraminal stenosis in rheumatoid arthritis. 2011 May STUDY DESIGN: Case-series study. OBJECTIVE: To describe the clinical presentation, characteristic findings of imaging studies, and treatment of lumbar radiculopathy caused by foraminal stenosis in rheumatoid arthritis. BACKGROUND. Lumbar lesions in rheumatoid arthritis are relatively rare, with a limited number of systemic reports. METHODS: Six patients with lumbar radiculopathy caused by foraminal stenosis in rheumatoid arthritis were treated. The patients were all women with a mean age of 69 years and mean rheumatoid arthritis duration of 15 years. The medical records and imaging studies of all patients were reviewed. RESULTS: The affected nerve roots were L4 in four patients and L3 in two patients. Foraminal stenosis was not demonstrated in magnetic resonance images in four of the six patients. Selective radiculography with nerve root block reproduced pain, manifested blocking effect, and demonstrated compression of the nerve root by the superior articular process of the lower vertebra in all patients. Conservative treatment was performed on one patient, and surgery was conducted for the rest of the five patients; radiculopathy was improved in all patients. CONCLUSIONS: Lumbar foraminal stenosis is a characteristic pathology of rheumatoid arthritis, and should be kept in mind in the diagnosis of lumbar radiculopathy. Selective radiculography is useful in the diagnosis of affected nerve roots.
19477615 MRI quantification of rheumatoid arthritis: current knowledge and future perspectives. 2009 Aug The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detecting and quantifying joint damage in RA. However, radiographs only show late disease manifestations as joint space narrowing and bone erosions, whereas it cannot detect synovitis and bone marrow oedema, i.e., inflammation in the synovium or the bone, which may be visualized by magnetic resonance imaging (MRI) months to years before erosions develop. Furthermore, MRI allows earlier visualization of bone erosions than radiography. In order to allow early treatment initiation and optimal guidance of the therapeutic strategy, there is a need for methods which are capable of early detection of inflammatory joint changes. In this review, we will discuss available data, advantages, limitations and potential future of MRI in RA.
20012974 [Current trends in the design and development of monoclonal antibodies against inflammator 2010 Feb As mediators of inflammation, cytokines contribute significantly to both the development and the extent of the inflammatory response in rheumatoid arthritis (RA). In addition, they regulate the differentiation of various cells involved in the pathogenesis of this disease. Tumour necrosis factor alpha (TNF alpha), interleukin (IL)-1 and IL-6 constitute prominent examples of such inflammatory cytokines and have been shown to play an important role in RA. As a consequence, the use of recombinant antibodies targeting these cytokines has revolutionized the treatment of RA. However, a considerable number of RA patients do not respond adequately to therapy with such biologics. Based on this notion, this article summarizes current trends in the design and development of monoclonal antibodies against inflammatory mediators. These include the identification of alterative target structures for anti-cytokine therapies, the specific modification of the antigen-binding CDR of therapeutic antibodies to reduce immunogenicity, alterations of the Fc part and the development of modified antibody fragments to improve the pharmacokinetics and to avoid non-specific immune reactions. Beyond that, efforts are undertaken to optimize the cost of these therapies.
18538830 Selective costimulation modulation with abatacept: a look at quality-of-life outcomes in p 2009 Jun OBJECTIVES: To highlight the importance of improving quality of life (QoL) in patients with rheumatoid arthritis (RA) and to provide a summary of the QoL benefits provided by abatacept in patients who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and/or tumor necrosis factor (TNF) antagonists. METHODS: A literature search of the MEDLINE, EMBASE, and BIOSIS databases was performed using the terms "abatacept," "cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)" and "ORENCIA," with the coindexing terms: "abatacept," "CTLA-4," and "ORENCIA." Only articles presenting primary data on QoL outcomes from randomized, placebo-controlled clinical trials of abatacept were included in the review. RESULTS: The literature search initially yielded 220 articles. A total of 8 articles fulfilled the inclusion criteria described above and are reviewed here. In clinical trials to date, abatacept treatment has been shown to improve QoL in patients who have an inadequate response to traditional DMARDs and TNF antagonists. CONCLUSIONS: Improvements in QoL are rated by patients as 1 of the most important benefits of an effective treatment; however, inclusion of QoL measurements in clinical trials as a measure of efficacy is a relatively recent event. Abatacept has been shown to alleviate both the physical and the emotional/social burdens that RA imposes on the patient, including improvements in day-to-day activity and reducing sleep problems and fatigue in patients with RA who have an inadequate response to DMARDs and/or TNF antagonists.
19888508 [Accuracy and standardization of diagnostic methods for the detection of antibodies to cit 2009 Jul Anti-citrullinated peptide antibodies (ACPA) have a very high specificity for rheumatoid arthritis, much more than that of the rheumatoid factor. In addition, ACPA can be found in sera in the pre-clinical phase, are associated with more severe joint destruction and with higher disease activity. In recent years, keeping pace with new knowledge and with progress made in the antigenic composition of tests and in the characterization of immunogenic epitopes, many immunoenzymatic (ELISA) methods of second and third generation have been produced and marketed commercially, and their use has spread among clinical laboratories. Today, completely automated methods are also available, which are easy to use and with a higher throughput, rendering the diagnostic utility of testing ever faster and more effective. This review takes into consideration the more important characteristics of the new ACPA-ELISA tests now commercially available, and also considers recent progress in standardizing test results.
20187969 Isolated talonavicular arthrodesis in patients with rheumatoid arthritis of the foot and t 2010 Feb 27 BACKGROUND: The foot is often affected in patients with rheumatoid arthritis. Subtalar joints are involved more frequently than ankle joints. Deformities of subtalar joints often lead to painful flatfoot and valgus deformity of the heel. Major contributors to the early development of foot deformities include talonavicular joint destruction and tibialis posterior tendon dysfunction, mainly due to its rupture. METHODS: Between 2002 and 2005 we performed isolated talonavicular arthrodesis in 26 patients; twenty women and six men. Tibialis posterior tendon dysfunction was diagnosed preoperatively by physical examination and by MRI. Talonavicular fusion was achieved via screws in eight patients, memory staples in twelve patients and a combination of screws and memory staples in six cases. The average duration of immobilization after the surgery was four weeks, followed by rehabilitation. Full weight bearing was allowed two to three months after surgery. RESULTS: The mean age of the group at the time of the surgery was 43.6 years. MRI examination revealed a torn tendon in nine cases with no significant destruction of the talonavicular joint seen on X-rays. Mean of postoperative followup was 4.5 years (3 to 7 years). The mean of AOFAS Hindfoot score improved from 48.2 preoperatively to 88.6 points at the last postoperative followup. Eighteen patients had excellent results (none, mild occasional pain), six patients had moderate pain of the foot and two patients had severe pain in evaluation with the score. Complications included superficial wound infections in two patients and a nonunion developed in one case. CONCLUSIONS: Early isolated talonavicular arthrodesis provides excellent pain relief and prevents further progression of the foot deformities in patients with rheumatoid arthritis and tibialis posterior tendon dysfunction.
19616965 Flow cytometric analysis of phospho-p38 mitogen-activated kinase (MAPK): p38 MAPK does not 2009 Sep BACKGROUND: The therapeutic effect of TNFalpha inhibition in rheumatoid arthritis (RA) is accompanied by an altered peripheral T cell cytokine profile, but the underlying mechanisms are not well known. In CD4+ T cells, TNF signalling includes the p38 MAP kinase (MAPK) pathway, which is also involved in proliferation and production of IL-4 and IFNgamma. METHODS: Phosphorylation of p38 MAPK was analysed flow cytometrically in peripheral blood mononuclear cells (PBMC) from healthy individuals and RA patients before and after adalimumab therapy. Cytokine production by CD3/CD28-stimulated PBMC was measured in the supernatant. RESULTS: Despite a transient activation of p38 MAPK in response to cellular stress from the cell separation, a significant decrease of spontaneous p38 MAPK phosphorylation was observed after adalimumab, compared to RA patients with active disease. Brief stimulation with TNFalpha/IL-1beta significantly activated p38 MAPK after but not before adalimumab therapy. In CD3/CD28-stimulated PBMC, significantly less p38 MAPK activation and increased IFNgamma production were observed after adalimumab therapy. CONCLUSION: In rheumatoid arthritis, adalimumab therapy decreases the phosphorylation of p38 MAPK except for its response to TNF/IL-1, while enhancing the production of IFNgamma. This suggests that p38 MAPK is not directly involved in the effect of TNF inhibition on cytokine production.